15 November 2025 : Review article
Signaling Pathways and Therapeutic Approaches in Post-Myocardial Infarction Fibrosis
Gen Ba ABCDEF 1*, Meiqiong Chen G 1DOI: 10.12659/MSM.949030
Med Sci Monit 2025; 31:e949030
Table 1 Preclinical evidence for different therapeutic approaches in post-MI fibrosis.
| Pathway | Strategy | Item | Reference | Year |
|---|---|---|---|---|
| TGF-β1 | Drug therapy | Sacubitril/valsartan | []3 | 2021 |
| Drug therapy | Empagliflozin | []4 | 2021 | |
| Drug therapy | Curcumin | []5 | 2021 | |
| Drug therapy | Caffeic acid | []6 | 2024 | |
| Drug therapy | Ethyl ferulate | []7 | 2023 | |
| Drug therapy | Icariin | []8 | 2023 | |
| Drug therapy | Calycosin | []9 | 2022 | |
| Drug therapy | Zerumbone | []10 | 2022 | |
| Drug therapy | Retinoid X receptor agonists | []11 | 2023 | |
| Drug therapy | Nutmeg-5 | []12 | 2022 | |
| Drug therapy | Guanxin V | []13 | 2022 | |
| Drug therapy | Dengzhan Shengmai capsule | []14 | 2023 | |
| Protein therapy | Apelin | []15 | 2024 | |
| Protein therapy | BMP1.3 | []16 | 2022 | |
| Protein therapy | CAV1 | []17 | 2024 | |
| Protein therapy | CD39 | []18 | 2024 | |
| Gene therapy | lncRNA MHRT | []19 | 2021 | |
| Gene therapy | MicroRNA-130a | []20 | 2022 | |
| Exercise | Exercise training | []21 | 2021 | |
| PI3K/AKT | Drug therapy | Liriodendrin | []24 | 2024 |
| Drug therapy | Emodin | []25 | 2024 | |
| Drug therapy | PQS | []26 | 2024 | |
| Gene therapy | MiR-199a-5p | []23 | 2023 | |
| Gene therapy | MiR-22 | []27 | 2024 | |
| STAT3 | Drug therapy | Hyperoside | []29 | 2024 |
| Drug therapy | Herbal formulas | []30 | 2024 | |
| Protein therapy | Nephronectin | []31 | 2022 | |
| Protein therapy | PCSK9 | []32 | 2024 | |
| Protein therapy | PTX3 KD | []33 | 2022 | |
| Exercise | Exercise | []34 | 2021 | |
| Gene therapy | CircularRNA Whsc1 | []35 | 2022 | |
| AMPK | Drug therapy | Isoliquiritigenin | []38 | 2024 |
| Drug therapy | DHA | []39 | 2022 | |
| Drug therapy | Empagliflozin | []40 | 2021 | |
| Drug therapy | Styrax | []41 | 2023 | |
| Protein therapy | Overexpression of HIF-1α | []42 | 2023 | |
| Protein therapy | Klotho | []43 | 2023 | |
| Exercise | Exercise | []44 | 2022 | |
| Nrf2 | Drug therapy | Fucoxanthin | []45 | 2023 |
| Drug therapy | Ghrelin | []46 | 2021 | |
| Drug therapy | Dietary capsaicin | []47 | 2024 | |
| Drug therapy | Urolithin A | []48 | 2022 | |
| Drug therapy | Tetrahydrocurcumin | []49 | 2023 | |
| Drug therapy | Protocatechuic acid | []50 | 2023 | |
| Drug therapy | Aloin | []51 | 2021 | |
| Protein therapy | BB-Cl-amidine | []52 | 2023 | |
| Protein therapy | Activation of SRC | []53 | 2024 | |
| Gene therapy | IRG1 | []54 | 2023 | |
| NF-κB | Cell therapy | Atorvastatin-induced tDC | []64 | 2023 |
| Drug therapy | Tubuloside A | []55 | 2024 | |
| Drug therapy | Chaihujialonggumuli granule | []56 | 2021 | |
| Gene therapy | Inhibition of miR-218-5p | []62 | 2021 | |
| Gene therapy | MSCs-EVs carrying microRNA-302d-3p | []63 | 2022 | |
| Protein therapy | Induced deficiency of Nur77 | []58 | 2021 | |
| Protein therapy | Induced deficiency of TRIM21 | []57 | 2023 | |
| Protein therapy | Knockout of USP38 | []59 | 2023 | |
| Protein therapy | Loss of α7nAChR | []60 | 2022 | |
| Protein therapy | Suppression of LAPTM5 | []61 | 2022 | |
| NLRP3 Inflammasome | Drug therapy | Phloretin | []67 | 2023 |
| Drug therapy | Celastrol | []71 | 2024 | |
| Drug therapy | Muscone | []70 | 2023 | |
| Drug therapy | Punicalagin | []69 | 2023 | |
| Drug therapy | Bufalin | []68 | 2023 | |
| Drug therapy | Xin-Li formula | []65 | 2023 | |
| Drug therapy | QishenYiqi dripping pill | []66 | 2022 | |
| Physical therapy | Hydrogen gas inhalation | []75 | 2021 | |
| Physical therapy | Therapeutic hypothermia | []76 | 2022 | |
| Protein therapy | Gefapixant | []73 | 2023 | |
| Protein therapy | M-CSF | []72 | 2023 | |
| Protein therapy | Myeloid-specific deletion of Capns1 | []74 | 2023 | |
| Wnt/β-catenin | Drug therapy | Lcz696 (Sacubitril/Valsartan) | []78 | 2021 |
| Drug therapy | XAV939 | []79 | 2024 | |
| Drug therapy | Linggui Zhugan Decoction | []80 | 2023 | |
| Gene therapy | MiR-145 | []81 | 2021 | |
| Protein therapy | Inhibition of ACP5 | []82 | 2024 | |
| MAPK | Drug therapy | Anshen Shumai Decoction | []93 | 2024 |
| Drug therapy | Optimized new Shengmai powder | []92 | 2023 | |
| Drug therapy | Astragaloside IV | []90 | 2021 | |
| Drug therapy | Peiminine | []91 | 2022 | |
| Protein therapy | OTUD7B (Cezanne) | []84 | 2022 | |
| Protein therapy | Knockdown of EPHB2 | []86 | 2024 | |
| Protein therapy | CTRP12 | []85 | 2023 | |
| Protein therapy | Knockdown of APEX1 | []87 | 2024 | |
| Protein therapy | Downregulation of IFIT3 | []88 | 2021 | |
| Protein therapy | Overexpression of ZNF418 | []89 | 2024 | |
| P53 | Drug therapy | Storax | []95 | 2022 |
| Drug therapy | Astragaloside IV | []96 | 2024 | |
| Gene therapy | Exosomal miR-218-5p/miR-363-3p | []98 | 2021 | |
| Protein therapy | Induced deficiency of LRRK2 | []97 | 2022 | |
| Protein therapy | Deletion of ASPP1 | []94 | 2024 | |
| TGF-β1+P53 | Protein therapy | CCL2 | []99 | 2024 |
| Protein therapy | A DUSP6 inhibitor | []100 | 2023 | |
| Protein therapy | Jatrorrhizine | []101 | 2022 | |
| Gene therapy | lncPostn | []102 | 2023 | |
| MAPK+PI3/AKT | Protein therapy | S100a8/a9 | []103 | 2022 |
| Protein therapy | ADAMTS8 | []104 | 2022 | |
| TGF-β1+MAPK | Protein therapy | RGS4 | []105 | 2021 |
| Gene therapy | MiR-19 | []106 | 2022 | |
| Wnt/β-catenin+PI3K/AKT | Protein therapy | Silencing DOCK2 | []107 | 2024 |
| STAT3+NF-κB | Drug therapy | Loganin | []108 | 2021 |
| Nrf2+PI3K/AKT | Drug therapy | Ginsenoside F2 | []109 | 2024 |
| NLRP3+NFκB | Drug therapy | ColCaNPs | []110 | 2022 |
| Drug therapy | Diannexin | []111 | 2024 | |
| Drug therapy | LuQi formula | []112 | 2022 | |
| Drug therapy | Buyang Huanwu Decoction | []113 | 2024 | |
| NLRP3+AMPK | Drug therapy | Resveratrol | []114 | 2024 |
| NLRP3+MAPK+NF-κB | Protein therapy | Inhibition of Sema4D (CD100) | []115 | 2024 |
| NLRP3+TGF-β1 | Exercise | Interval training | []116 | 2024 |
| MI – myocardial infarction; TGF-β1 – transforming growth factor-β1; PI3K – phosphatidylinositol 3-kinase; AKT – protein kinase B; STAT – signal transducer and activator of transcription; AMPK – AMP-activated protein kinase; Nrf2 – Nuclear factor erythroid 2-related factor 2; NF-κB – nuclear factor kappa B; NLRP3 – the nucleotide-binding domain, leucine-rich-repeat family, pyrin domain-containing 3; MAPK – mitogen-activated protein kinase; BMP1.3 – bone morphogenetic protein 1.3; CAV1 – caveolin-1 protein; CD39 – ectonucleoside triphosphate diphosphohydrolase-1; lncRNA – long-chain noncoding RNA; MHRT – myosin heavy-chain associated RNA transcript; PQS – Panax Quinquefolium Saponins; PCSK9 – proprotein convertase subtilisin/kexin type 9; PTX3 KD – depletion of Pentraxin 3; DHA – docosahexaenoic acid; HIF-1α – hypoxia inducible factor-1α; SRC – steroid receptor coactivator; IRG1 – immune responsive gene 1; tDC – tolerogenic dendritic cells; MSCs-EVs carrying – mesenchymal stem cell-derived extracellular vesicle-shuttled; TRIM21 – Tripartite motif-containing protein 21; USP38 – ubiquitin-specific protease 38; α7nAChR – α7 nicotinic acetylcholine receptor; LAPTM5 – lysosomal-associated protein transmembrane 5; M-CSF – macrophage colony-stimulating factor; ACP5 – acid phosphatase 5; EPHB2 – erythropoietin hepatocellular receptor B2; CTRP12 – C1q/tumor necrosis factor-related protein 12; APEX1 – apurinic/apyrimidinic endodeoxyribonuclease 1; IFIT3 – tetratricopeptide repeats 3; ZNF418 – zinc-finger protein 418; LRRK2 –leucine-rich repeat kinase 2; ASPP1 – apoptosis stimulating protein of p53 protein 1; CCL2 – C-C motif chemokine 2; DUSP6 – dual-specificity phosphatase 6; ADAMTS8 – a disintegrin and metalloproteinase with thrombospondin motifs 8; RGS – regulators of G protein signaling; DOCK2 – the dedicator of cytokinesis 2; ColCaNPs – colchicine-containing nanoparticles. | ||||